Publications (79)
Proofreading through spatial gradients
Vahe Galstyan, Kabir Husain, Fangzhou Xiao +2
Key enzymatic processes in biology use the nonequilibrium error correction mechanism called kinetic proofreading to enhance their specificity. Kinetic proofreading typically requir…
Harnessing Avidity: Quantifying Entropic and Energetic Effects of Linker Length and Rigidity Required for Multivalent Binding of Antibodies to HIV-1 Spikes
Tal Einav, Shahrzad Yazdi, Aaron Coey +2
Due to the low density of envelope (Env) spikes on the surface of HIV-1, neutralizing IgG antibodies rarely bind bivalently using both antigen-binding arms (Fabs) to crosslink betw…
The Role of Lipid Bilayer Mechanics in Mechanosensation
Tristan Ursell, Rob Phillips, Jane' Kondev +2
Mechanosensation is a key part of the sensory repertoire of a vast array of different cells and organisms. The molecular dissection of the origins of mechanosensation is rapidly ad…
First-principles calculation of DNA looping in tethered particle experiments
Kevin B. Towles, John F. Beausang, Hernan G. Garcia +2
We calculate the probability of DNA loop formation mediated by regulatory proteins such as Lac repressor (LacI), using a mathematical model of DNA elasticity. Our model is adapted…
The Environment-Dependent Regulatory Landscape of the E. coli Genome
Tom Röschinger, Heun Jin Lee, Rosalind Wenshan Pan +7
All cells respond to changes in both their internal milieu and the environment around them through the regulation of their genes. Despite decades of effort, there remain huge gaps…
Geometry-Dependent Defect Merging Induces Bifurcated Dynamics in Active Networks
Fan Yang, Shichen Liu, Hao Wang +3
Cytoskeletal networks can repair defects to maintain structural integrity. However, the mechanisms and dynamics of defect merging remain poorly understood. Here we report a geometr…
Modeling and mechanical perturbations reveal how spatially regulated anchorage gives rise to spatially distinct mechanics across the mammalian spindle
Pooja Suresh, Vahe Galstyan, Rob Phillips +1
During cell division, the spindle generates force to move chromosomes. In mammals, microtubule bundles called kinetochore-fibers (k-fibers) attach to and segregate chromosomes. To…
Motor-driven microtubule diffusion in a photobleached dynamical coordinate system
Soichi Hirokawa, Heun Jin Lee, Rachel A Banks +4
Motor-driven cytoskeletal remodeling in cellular systems can often be accompanied by a diffusive-like effect at local scales, but distinguishing the contributions of the ordering p…
Wildebeest Herds on Rolling Hills: Flocking on Arbitrary Curved Surfaces
Christina L. Hueschen, Alexander R. Dunn, Rob Phillips
The collective behavior of active agents, whether herds of wildebeest or microscopic actin filaments propelled by molecular motors, is an exciting frontier in biological and soft m…
Programming Boundary Deformation Patterns in Active Networks
Zijie Qu, Jialong Jiang, Heun Jin Lee +3
Active materials take advantage of their internal sources of energy to self-organize in an automated manner. This feature provides a novel opportunity to design micron-scale machin…
Measurement of FLux Fluctuations in Diffusion in the Small-Numbers Limit
Effrosyni Seitaridou, Mandar M. Inamdar, Rob Phillips +2
Using a microfluidics device filled with a colloidal suspension of microspheres, we test the laws of diffusion in the limit of small particle numbers. Our focus is not just on aver…
Sequence Dependence of Transcription Factor-Mediated DNA Looping
Stephanie Johnson, Martin Lindén, Rob Phillips
DNA is subject to large deformations in a wide range of biological processes. Two key examples illustrate how such deformations influence the readout of the genetic information: th…
A minimal scenario for the origin of non-equilibrium order
Riccardo Ravasio, Kabir Husain, Constantine G. Evans +4
Life uses non-equilibrium mechanisms to create ordered structures not attainable at equilibrium; the resulting order is assumed to provide functional benefits that outweigh costs o…
Figure 1 Theory Meets Figure 2 Experiments in the Study of Gene Expression
Rob Phillips, Nathan M. Belliveau, Griffin Chure +3
It is tempting to believe that we now own the genome. The ability to read and re-write it at will has ushered in a stunning period in the history of science. Nonetheless, there is…
How the Avidity of Polymerase Binding to the -35/-10 Promoter Sites Affects Gene Expression
Tal Einav, Rob Phillips
Although the key promoter elements necessary to drive transcription in Escherichia coli have long been understood, we still cannot predict the behavior of arbitrary novel promoters…
Elastic energy of polyhedral bilayer vesicles
Christoph A. Haselwandter, Rob Phillips
In recent experiments [M. Dubois, B. Demé, T. Gulik-Krzywicki, J.-C. Dedieu, C. Vautrin, S. Désert, E. Perez, and T. Zemb, Nature (London) Vol. 411, 672 (2001)] the spontaneous f…
Excluded-Volume Effects in Tethered-Particle Experiments: Bead Size Matters
Darren E. Segall, Phillip C. Nelson, Rob Phillips
The tethered-particle method is a single-molecule technique that has been used to explore the dynamics of a variety of macromolecules of biological interest. We give a theoretical…
Membrane-protein interactions in mechanosensitive channels
Paul Wiggins, Rob Phillips
In this paper, we examine the mechanical role of the lipid bilayer in ion channel conformation and function with specific reference to the case of the mechanosensitive channel of l…
Dynamics of DNA Ejection From Bacteriophage
Mandar M. Inamdar, William M. Gelbart, Rob Phillips
The ejection of DNA from a bacterial virus (``phage'') into its host cell is a biologically important example of the translocation of a macromolecular chain along its length throug…
Transcriptional Regulation by the Numbers 2: Applications
Lacramioara Bintu, Nicolas E. Buchler, Hernan G. Garcia +5
With the increasing amount of experimental data on gene expression and regulation, there is a growing need for quantitative models to describe the data and relate them to the diffe…
A quantitative compendium of COVID-19 epidemiology
Yinon M. Bar-On, Ron Sender, Avi I. Flamholz +2
Accurate numbers are needed to understand and predict viral dynamics. Curation of high-quality literature values for the infectious period duration or household secondary attack ra…
Analysis of Inducer and Operator Binding for Cyclic-AMP Receptor Protein Mutants
Tal Einav, Julia Duque, Rob Phillips
Allosteric transcription factors undergo binding events both at their inducer binding sites as well as at distinct DNA binding domains, and it is often difficult to disentangle the…
The Anthropocene by the Numbers: A Quantitative Snapshot of Humanity's Influence on the Planet
Griffin Chure, Rachel A. Banks, Avi I. Flamholz +6
The presence and action of humans on Earth has exerted a strong influence on the evolution of the planet over the past 10,000 years, the consequences of which are now bec…
Multiple Lac-mediated loops revealed by Bayesian statistics and tethered particle motion
Stephanie Johnson, Jan-Willem van de Meent, Rob Phillips +2
The bacterial transcription factor LacI loops DNA by binding to two separate locations on the DNA simultaneously. Despite being one of the best-studied model systems for transcript…
Analytic models for mechanotransduction: gating a mechanosensitive channel
Paul Wiggins, Rob Phillips
Analytic estimates for the forces and free energy generated by bilayer deformation reveal a compelling and intuitive model for MscL channel gating analogous to the nucleation of a…
Deciphering regulatory architectures from synthetic single-cell expression patterns
Rosalind Wenshan Pan, Tom Roeschinger, Kian Faizi +2
For the vast majority of genes in sequenced genomes, there is limited understanding of how they are regulated. Without such knowledge, it is not possible to perform a quantitative…
Effect of promoter architecture on the cell-to-cell variability in gene expression
Alvaro Sanchez, Hernan Garcia, Daniel Jones +2
According to recent experimental evidence, the architecture of a promoter, defined as the number, strength and regulatory role of the operators that control the promoter, plays a m…
An equivalence between a Maximum Caliber analysis of two-state kinetics and the Ising model
Sarah Marzen, Dave Wu, Mandar Inamdar +1
Application of the information-theoretic Maximum Caliber principle to the microtrajectories of a two-state system shows that the determination of key dynamical quantities can be ma…
Design Principles of Length Control of Cytoskeletal Structures
Lishibanya Mohapatra, Bruce L. Goode, Predrag Jelenkovic +2
Cells contain elaborate and interconnected networks of protein polymers which make up the cytoskeleton. The cytoskeleton governs the internal positioning and movement of vesicles a…
Informational blueprints reveal condition-dependent gene regulatory architectures
Doruk Efe Gökmen, Rosalind Wenshan Pan, Tom Röschinger +4
While coding regions in the genome have a direct interpretation in terms of protein products, significant fractions are non-coding and yet control essential biological functions. U…
First-principles prediction of the information processing capacity of a simple genetic circuit
Manuel Razo-Mejia, Sarah Marzen, Griffin Chure +3
Given the stochastic nature of gene expression, genetically identical cells exposed to the same environmental inputs will produce different outputs. This heterogeneity has been hyp…
Combinatorial Control through Allostery
Vahe Galstyan, Luke Funk, Tal Einav +1
Many instances of cellular signaling and transcriptional regulation involve switch-like molecular responses to the presence or absence of input ligands. To understand how these res…
Schrödinger's "What is Life?" at 75
Rob Phillips
2019 marked the 75th anniversary of the publication of Erwin Schrödinger's "What is Life?", a short book described by Roger Penrose in his preface to a reprint of this classic as…
Allostery and Kinetic Proofreading
Vahe Galstyan, Rob Phillips
Kinetic proofreading is an error correction mechanism present in the processes of the central dogma and beyond, and typically requires the free energy of nucleotide hydrolysis for…
Forces During Bacteriophage DNA Packaging and Ejection
Prashant K. Purohit, Mandar M. Inamdar, Paul D. Grayson +3
The conjunction of insights from structural biology, solution biochemistry, genetics and single molecule biophysics has provided a renewed impetus for the construction of quantitat…
A Non-Local Formulation of the Peierls Dislocation Model
Ron Miller, Rob Phillips, Glenn Beltz +1
Cohesive zone models provide an illuminating and tractable way to include constitutive nonlinearity into continuum models of defects. Powerful insights have been gained by studying…
A trajectory approach to two-state kinetics of single particles on sculpted energy landscapes
David Wu, Kingshuk Ghosh, Mandar Inamdar +4
We study the trajectories of a single colloidal particle as it hops between two energy wells A and B, which are sculpted using adjacent optical traps by controlling their respectiv…
Biological Consequences of Tightly Bent DNA: The Other Life of a Macromolecular Celebrity
Hernan G. Garcia, Paul Grayson, Lin Han +6
The mechanical properties of DNA play a critical role in many biological functions. For example, DNA packing in viruses involves confining the viral genome in a volume (the viral c…
Persistent fluid flows defined by active matter boundaries
Zijie Qu, Dominik Schildknecht, Shahriar Shadkhoo +5
Biological systems achieve precise control over ambient fluids through the self-organization of active protein structures including flagella, cilia, and cytoskeletal networks. In a…
Statistical Mechanics of Allosteric Enzymes
Tal Einav, Linas Mazutis, Rob Phillips
The concept of allostery in which macromolecules switch between two different conformations is a central theme in biological processes ranging from gene regulation to cell signalin…
Transcriptional Regulation by the Numbers 1: Models
Lacramioara Bintu, Nicolas E. Buchler, Hernan G. Garcia +4
The study of gene regulation and expression is often discussed in quantitative terms. In particular, the expression of genes is regularly characterized with respect to how much, ho…
A First Exposure to Statistical Mechanics for Life Scientists
Hernan G. Garcia, Jané Kondev, Nigel Orme +2
Statistical mechanics is one of the most powerful and elegant tools in the quantitative sciences. One key virtue of statistical mechanics is that it is designed to examine large sy…
Boundaries Program Deformation in Isolated Active Networks
Zixiang Lin, Shichen Liu, Shahriar Shadkhoo +9
Cellular structures must organize themselves within strict physical constraints, operating with finite resources and well-defined boundaries. Classical systems demonstrate only pas…
DNA sequence-dependent mechanics and protein-assisted bending in repressor-mediated loop formation
James Q. Boedicker, Hernan G. Garcia, Stephanie Johnson +1
As the chief informational molecule of life, DNA is subject to extensive physical manipulations. The energy required to deform double-helical DNA depends on sequence, and this mech…
Dynamic Flow Control Through Active Matter Programming Language
Fan Yang, Shichen Liu, Heun Jin Lee +2
Cells control fluid flows with a spatial and temporal precision that far exceeds the capabilities of current microfluidic technologies. Cells achieve this superior spatio-temporal…
Reconciling Kinetic and Equilibrium Models of Bacterial Transcription
Muir J. Morrison, Manuel Razo-Mejia, Rob Phillips
The study of transcription remains one of the centerpieces of modern biology with implications in settings from development to metabolism to evolution to disease. Precision measure…
Quantitative clarification of key questions about COVID-19 epidemiology
Yinon M. Bar-On, Ron Sender, Avi I. Flamholz +2
Modeling the spread of COVID-19 is crucial for informing public health policy. All models for COVID-19 epidemiology rely on parameters describing the dynamics of the infection proc…
Tuning transcriptional regulation through signaling: A predictive theory of allosteric induction
Manuel Razo-Mejia, Stephanie L. Barnes, Nathan M. Belliveau +4
Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its…
Exact theory of kinkable elastic polymers
Paul A. Wiggins, Rob Phillips, Philip C. Nelson
The importance of nonlinearities in material constitutive relations has long been appreciated in the continuum mechanics of macroscopic rods. Although the moment (torque) response…
Connecting the dots between mechanosensitive channel abundance, osmotic shock, and survival at single-cell resolution
Griffin Chure, Heun Jin Lee, Rob Phillips
Rapid changes in extracellular osmolarity are one of many insults microbial cells face on a daily basis. To protect against such shocks, Escherichia coli and other microbes express…
Lipid Domain Order and the Algebra of Morphology
Tristan Ursell, Rob Phillips
Lipid membranes regulate the flow of materials and information between cells and their organelles. Further, lipid composition and morphology can play a key role in regulating a var…
Controlling Organization and Forces in Active Matter Through Optically-Defined Boundaries
Tyler D. Ross, Heun Jin Lee, Zijie Qu +3
Living systems are capable of locomotion, reconfiguration, and replication. To perform these tasks, cells spatiotemporally coordinate the interactions of force-generating, "active"…
A Single-Molecule Hershey-Chase Experiment
David Van Valen, David Wu, Yi-Ju Chen +3
Ever since Hershey and Chase used phages to establish DNA as the carrier of genetic information in 1952, the precise mechanisms of phage DNA translocation have been a mystery. Whil…
Bifurcations and multistability in inducible three-gene toggle switch networks
Rebecca J. Rousseau, Rob Phillips
Control of transcription presides over a vast array of biological processes, including those mediated by gene regulatory circuits that exhibit multistability. Within these circuits…
Poly(dA:dT)-rich DNAs are highly flexible in the context of DNA looping
Stephanie Johnson, Yi-Ju Chen, Rob Phillips
Large-scale DNA deformation is ubiquitous in transcriptional regulation in prokaryotes and eukaryotes alike. Though much is known about how transcription factors and constellations…
Conditioning as a route to stereotyped behavior in growing populations
Riccardo Ravasio, Kabir Husain, Constantine G. Evans +4
Biological systems perform complex multi-step processes in a reproducible way despite underlying stochasticity. The standard explanation is micromanagement by molecular machinery t…
SARS-CoV-2 (COVID-19) by the numbers
Yinon M. Bar-On, Avi I. Flamholz, Rob Phillips +1
The current SARS-CoV-2 pandemic is a harsh reminder of the fact that, whether in a single human host or a wave of infection across continents, viral dynamics is often a story about…
Force Propagation in Active Cytoskeletal Networks
Shichen Liu, Rosalind Wenshan Pan, Heun Jin Lee +6
In biological systems, molecular-scale forces and motions are pivotal for enabling processes like motility, shape change, and replication. These forces and motions are organized, a…
Lattice Resistance and Peierls Stress in Finite-size Atomistic Dislocation Simulations
David L. Olmsted, Kedar Y. Hardikar, Rob Phillips
Atomistic computations of the Peierls stress in fcc metals are relatively scarce. By way of contrast, there are many more atomistic computations for bcc metals, as well as mixed di…
Modulation of DNA loop lifetimes by the free energy of loop formation
Yi-Ju Chen, Stephanie Johnson, Peter Mulligan +2
Storage and retrieval of the genetic information in cells is a dynamic process that requires the DNA to undergo dramatic structural rearrangements. DNA looping is a prominent examp…
Deciphering the regulatory genome of , one hundred promoters at a time
William T. Ireland, Suzannah M. Beeler, Emanuel Flores-Bautista +5
Advances in DNA sequencing have revolutionized our ability to read genomes. However, even in the most well-studied of organisms, the bacterium , for $\appro…
The Energetics of Molecular Adaptation in Transcriptional Regulation
Griffin Chure, Manuel Razo-Mejia, Nathan M. Belliveau +5
Mutation is a critical mechanism by which evolution explores the functional landscape of proteins. Despite our ability to experimentally inflict mutations at will, it remains diffi…
The Energetic Cost of Building a Virus
Gita Mahmoudabadi, Ron Milo, Rob Phillips
Viruses are incapable of autonomous energy production. Although many experimental studies make it clear that viruses are parasitic entities that hijack the host's molecular resourc…
Finite Sized Atomistic Simulations of Screw Dislocations
Vijay B. Shenoy, Rob Phillips
The interaction of screw dislocations with an applied stress is studied using atomistic simulations in conjunction with a continuum treatment of the role played by the far field bo…
Force steps during viral DNA packaging ?
Prashant K. Purohit, Jane' Kondev, Rob Phillips
Biophysicists and structural biologists increasingly acknowledge the role played by the mechanical properties of macromolecules as a critical element in many biological processes.…
The effect of genome length on ejection forces in bacteriophage lambda
Paul Grayson, Alex Evilevitch, Mandar M. Inamdar +4
A variety of viruses tightly pack their genetic material into protein capsids that are barely large enough to enclose the genome. In particular, in bacteriophages, forces as high a…
Directional interactions and cooperativity between mechanosensitive membrane proteins
Christoph A. Haselwandter, Rob Phillips
While modern structural biology has provided us with a rich and diverse picture of membrane proteins, the biological function of membrane proteins is often influenced by the mechan…
Teaching the Principles of Statistical Dynamics
Kingshuk Ghosh, Ken Dill, Mandar M. Inamdar +2
We describe a simple framework for teaching the principles that underlie the dynamical laws of transport: Fick's law of diffusion, Fourier's law of heat flow, the Newtonian viscosi…
Morphology and Interaction between Lipid Domains
Tristan S. Ursell, William S. Klug, Rob Phillips
Cellular membranes are a heterogeneous mix of lipids, proteins and small molecules. Special groupings of saturated lipids and cholesterol form a liquid-ordered phase, known as `lip…
The Dynamics of Inducible Genetic Circuits
Zitao Yang, Rebecca J. Rousseau, Sara D. Mahdavi +2
Genes are connected in complex networks of interactions where often the product of one gene is a transcription factor that alters the expression of another. Many of these networks…
Biological Processes as Exploratory Dynamics
Jane Kondev, Marc Kirschner, Hernan G. Garcia +2
Many biological processes can be thought of as the result of an underlying dynamics in which the system repeatedly undergoes distinct and abortive trajectories with the dynamical p…
Minimal Bending Energies of Bilayer Polyhedra
Christoph A. Haselwandter, Rob Phillips
Motivated by recent experiments on bilayer polyhedra composed of amphiphilic molecules, we study the elastic bending energies of bilayer vesicles forming polyhedral shapes. Allowin…
Many Will Enter, Few Will Win: Cost and Sensitivity of Exploratory Dynamics
Elena F Koslover, Milo M Lin, Rob Phillips
A variety of biomolecular systems rely on exploratory dynamics to reach target locations or states within a cell. Without a mechanism to remotely sense and move directly towards a…
Membranes by the Numbers
Rob Phillips
Many of the most important processes in cells take place on and across membranes. With the rise of an impressive array of powerful quantitative methods for characterizing these mem…
Monod-Wyman-Changeux Analysis of Ligand-Gated Ion Channel Mutants
Tal Einav, Rob Phillips
We present a framework for computing the gating properties of ligand-gated ion channel mutants using the Monod-Wyman-Changeux (MWC) model of allostery. We derive simple analytic fo…
Entropic Tension in Crowded Membranes
Martin Lindén, Pierre Sens, Rob Phillips
Unlike their model membrane counterparts, biological membranes are richly decorated with a heterogeneous assembly of membrane proteins. These proteins are so tightly packed that th…
Cooperative Gating and Spatial Organization of Membrane Proteins through Elastic Interactions
Tristan Ursell, Kerwyn Huang, Eric Peterson +1
Biological membranes are elastic media in which the presence of a transmembrane protein leads to local bilayer deformation. The energetics of deformation allow two membrane protein…
Concentration and Length Dependence of DNA Looping in Transcriptional Regulation
Lin Han, Hernan G. Garcia, Seth Blumberg +4
In many cases, transcriptional regulation involves the binding of transcription factors at sites on the DNA that are not immediately adjacent to the promoter of interest. This acti…
Ion-dependent dynamics of DNA ejections for bacteriophage lambda
David Wu, David Van Valen, Qicong Hu +1
We study the control parameters that govern the dynamics of in vitro DNA ejection in bacteriophage lambda. Past work has demonstrated that bacteriophage DNA is highly pressurized;…